EA032003B1 - Анти-tdp-43 антитело - Google Patents
Анти-tdp-43 антитело Download PDFInfo
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- EA032003B1 EA032003B1 EA201490825A EA201490825A EA032003B1 EA 032003 B1 EA032003 B1 EA 032003B1 EA 201490825 A EA201490825 A EA 201490825A EA 201490825 A EA201490825 A EA 201490825A EA 032003 B1 EA032003 B1 EA 032003B1
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CN (1) | CN104159918B (hr) |
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Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL199534A (en) | 2007-01-05 | 2013-01-31 | Univ Zuerich | An isolated human antibody capable of detecting a neoepitope in a disease-related protein, a polynucleotide encoding an antibody, a vector containing the polynucleotide, a host cell containing the polynucleotide or vector, a preparation containing the antibody and related methods and uses. |
BR112014010161B1 (pt) | 2011-10-28 | 2022-02-08 | Biogen International Neuroscience Gmbh | Anticorpo anti-proteína tar de ligação ao dna que possui 43 kda (tdp-43), seu método de preparação e seu uso, composições, polinucleotídeos, vetor, e kit útil no diagnóstico ou monitoramento da progressão de uma proteinopatia de tdp-43 |
CA2914831C (en) | 2013-06-11 | 2022-10-11 | Paul Scherrer Institut | Method for determining mutateable ligand-gpcr binding at single amino acid resolution and pairs of mutated ligand and gpcr |
WO2015117088A2 (en) | 2014-01-31 | 2015-08-06 | Arizona Board Of Regents On Behalf Of Arizona State University | Antibody based reagents that specifically recognize neurodegenerative disease related forms of the protein tdp-43 |
MX2017001285A (es) | 2014-07-29 | 2017-04-25 | Neurimmune Holding Ag | Anticuerpos anti-huntingtina (htt) derivados de humano y usos de los mismos. |
CN104497121A (zh) * | 2014-08-29 | 2015-04-08 | 苏州顺升桥生物科技有限公司 | 淀粉样蛋白tdp-43及其用途 |
TWI592423B (zh) * | 2014-10-03 | 2017-07-21 | 中央研究院 | 可辨識致病性tdp-43之抗體及其用途 |
WO2016053610A1 (en) * | 2014-10-03 | 2016-04-07 | Academia Sinica | Antibodies against pathological forms of tdp-43 and uses thereof |
US9796778B1 (en) | 2014-10-03 | 2017-10-24 | Academia Sinica | Antibodies against pathological forms of TDP-43 and uses thereof |
MA41115A (fr) | 2014-12-02 | 2017-10-10 | Biogen Int Neuroscience Gmbh | Procédé de traitement de la maladie d'alzheimer |
WO2017111166A1 (ja) * | 2015-12-25 | 2017-06-29 | 国立大学法人東京農工大学 | Tdp-43細胞内存在量関連疾患治療剤 |
PL3430397T3 (pl) | 2016-03-14 | 2022-04-04 | Biogen International Neuroscience Gmbh | Oznaczenie fagocytozy zależnej od przeciwciał do wiarygodnych pomiarów wychwytu zagregowanych białek |
MA45715A (fr) | 2016-07-25 | 2019-05-29 | Biogen Ma Inc | Anticorps anti-hspa5 (grp78) et leurs utilisations |
US20200031895A1 (en) | 2016-12-16 | 2020-01-30 | Biogen Ma Inc. | Stabilized proteolytically activated growth differentiation factor 11 |
CN110740749A (zh) * | 2017-03-14 | 2020-01-31 | 戊瑞治疗有限公司 | 在酸性pH下与VISTA结合的抗体 |
CA3064785A1 (en) * | 2017-05-30 | 2018-12-06 | The University Of British Columbia | Epitopes in the rna recognition motif 1 (rrm1) of tdp-43 and misfolding-selective antibodies thereto |
CN118370815A (zh) | 2017-08-22 | 2024-07-23 | 渤健马萨诸塞州股份有限公司 | 含有抗β淀粉样蛋白抗体的药物组合物 |
EP3724232A4 (en) | 2017-12-14 | 2021-12-15 | The University of Ottawa | EXOSOME PACKAGING AND TARGETED AUTOPHAGY |
WO2019118527A1 (en) * | 2017-12-14 | 2019-06-20 | The Johns Hopkins University | Novel anti-fungal inhibitors |
WO2019134981A1 (en) * | 2018-01-05 | 2019-07-11 | Ac Immune Sa | Misfolded tdp-43 binding molecules |
EP3770262A4 (en) | 2018-03-16 | 2021-12-15 | National University Corporation Shiga University of Medical Science | ANTIBODY FRAGMENT DEGRADING AND ELIMINATING ABNORMAL TDP-43 |
TW202019398A (zh) * | 2018-06-28 | 2020-06-01 | 張翔毓 | 用於治療或預防構形疾病之方法及藥物篩選方法 |
CN113508135A (zh) | 2018-10-29 | 2021-10-15 | 比奥根Ma公司 | 增强血脑屏障转运的人源化和稳定化的fc5变体 |
AU2019399680A1 (en) * | 2018-12-14 | 2021-07-15 | Promis Neurosciences Inc. | Antibodies to misfolded TDP-43 and methods of use |
JP2022533432A (ja) | 2019-05-23 | 2022-07-22 | エイシー イミューン ソシエテ アノニム | 抗tdp-43結合分子およびその使用 |
EP4013773A4 (en) * | 2019-08-12 | 2023-08-23 | Macquarie University | COMPOSITIONS AND METHODS OF TREATMENT |
GB202004863D0 (en) * | 2020-04-02 | 2020-05-20 | Univ Oxford Innovation Ltd | Method |
KR20230025659A (ko) | 2020-04-28 | 2023-02-22 | 솔라 바이오사이언시즈 엘엘씨 | Tdp-43 단백질병증의 치료를 위한 조성물 및 방법 |
WO2021217267A1 (en) * | 2020-04-29 | 2021-11-04 | The University Of British Columbia | Single chain antibodies and intrabodies to misfolded tdp-43 and methods of use |
EP4175716A4 (en) * | 2020-07-06 | 2024-08-21 | Univ Texas | TDP-43 BIOSENSOR CELL LINES |
JP2023537761A (ja) | 2020-08-14 | 2023-09-05 | エイシー イミューン ソシエテ アノニム | ヒト化抗tdp-43結合分子およびその使用 |
EP4252243A2 (en) | 2020-11-30 | 2023-10-04 | Enigma Biointelligence, Inc. | Non-invasive assessment of alzheimer's disease |
CN112920264B (zh) * | 2021-02-08 | 2022-07-05 | 武汉大学 | Tdp-43蛋白的o-糖基化突变体及其应用 |
JP6961278B1 (ja) * | 2021-03-10 | 2021-11-05 | 国立研究開発法人量子科学技術研究開発機構 | 生体試料中のtdp−43を測定する方法及び装置 |
JP2024520414A (ja) * | 2021-05-27 | 2024-05-24 | メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ | タンパク質症を処置する方法及び材料 |
US20230107901A1 (en) * | 2021-10-01 | 2023-04-06 | University Of Utah Research Foundation | Pathologic tdp-43 as a biomarker for the diagnosis of tdp-43 proteinopathy |
CA3239708A1 (en) | 2021-12-03 | 2023-06-08 | Aubin MICHALON | Novel potency assay for antibody-based drugs and useful means therefor |
TW202342519A (zh) | 2022-02-16 | 2023-11-01 | 瑞士商Ac 免疫有限公司 | 人源化抗tdp-43結合分子及其用途 |
WO2023194565A1 (en) * | 2022-04-08 | 2023-10-12 | Ac Immune Sa | Anti-tdp-43 binding molecules |
WO2023205579A1 (en) * | 2022-04-18 | 2023-10-26 | The Regents Of The University Of California | Compositions and methods for disrupting pathological aggregates |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5688511A (en) * | 1991-11-05 | 1997-11-18 | Board Of Regents, The University Of Texas System | Cellular protein TDP-43 and regulation of HIV-1 gene expression |
WO2008081008A1 (en) * | 2007-01-05 | 2008-07-10 | University Of Zurich | Method of providing disease-specific binding molecules and targets |
WO2009099941A2 (en) * | 2008-02-01 | 2009-08-13 | Washington University In St. Louis | Sequences associated with tdp-43 proteinopathies and methods of using the same |
CN101634656A (zh) * | 2009-08-21 | 2010-01-27 | 武汉三鹰生物技术有限公司 | 人tdp-43的单抗包被酶标板的制法及elisa检测试剂盒 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0934953A2 (en) | 1997-12-03 | 1999-08-11 | Boehringer Mannheim Corporation | Complex specific antibodies, method of preparation and uses thereof |
US8354236B2 (en) * | 2006-09-29 | 2013-01-15 | The Trustees Of The University Of Pennsylvania | Detection of neurodegenerative disease |
WO2008151055A1 (en) | 2007-06-01 | 2008-12-11 | Mayo Foundation For Medical Education And Research | Diagnosing neurodegenerative diseases |
JP5439176B2 (ja) * | 2007-07-06 | 2014-03-12 | 公益財団法人東京都医学総合研究所 | Tdp−43凝集物に特異的に結合する抗体 |
ES2544569T3 (es) | 2008-12-19 | 2015-09-01 | Biogen International Neuroscience Gmbh | Autoanticuerpos humanos anti alfa-sinucleina |
BR112014010161B1 (pt) | 2011-10-28 | 2022-02-08 | Biogen International Neuroscience Gmbh | Anticorpo anti-proteína tar de ligação ao dna que possui 43 kda (tdp-43), seu método de preparação e seu uso, composições, polinucleotídeos, vetor, e kit útil no diagnóstico ou monitoramento da progressão de uma proteinopatia de tdp-43 |
-
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- 2019-02-25 US US16/284,602 patent/US11091540B2/en active Active
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5688511A (en) * | 1991-11-05 | 1997-11-18 | Board Of Regents, The University Of Texas System | Cellular protein TDP-43 and regulation of HIV-1 gene expression |
WO2008081008A1 (en) * | 2007-01-05 | 2008-07-10 | University Of Zurich | Method of providing disease-specific binding molecules and targets |
WO2009099941A2 (en) * | 2008-02-01 | 2009-08-13 | Washington University In St. Louis | Sequences associated with tdp-43 proteinopathies and methods of using the same |
CN101634656A (zh) * | 2009-08-21 | 2010-01-27 | 武汉三鹰生物技术有限公司 | 人tdp-43的单抗包被酶标板的制法及elisa检测试剂盒 |
Non-Patent Citations (4)
Title |
---|
"Biogen Idec and Neurimmune Announce Agreement on Three Neurodegenerative Disease Programs", 20 December 2010 (2010-12-20), XP055064808, Retrieved from the Internet: URL:http://www.businesswire.com/news/home/20101220006526/en/Biogen-Idec-Neurimmune-Announce-Agreement-Neurodegenerative-Disease [retrieved on 2013-05-31], the whole document * |
"TARDBP (41-7.1): sc-100871", 26 March 2009 (2009-03-26), XP055064934, Retrieved from the Internet: URL:http://datasheets.scbt.com/sc-100871.pdf [retrieved on 2013-06-03], the whole document * |
JOHNSON B.S. ET AL.,: "a yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, NATIONAL ACADEMY OF SCIENCES, US, vol. 105, no. 17, 29 April 2008 (2008-04-29), US, pages 6439 - 6444, XP002534604, ISSN: 0027-8424, DOI: 10.1073/PNAS.0802082105 * |
YUKI SHIINA ; KUNIMASA ARIMA ; HIROKO TABUNOKI ; JUN-ICHI SATOH: "TDP-43 Dimerizes in Human Cells in Culture", CELLULAR AND MOLECULAR NEUROBIOLOGY, KLUWER ACADEMIC PUBLISHERS-PLENUM PUBLISHERS, NE, vol. 30, no. 4, 31 December 2009 (2009-12-31), Ne, pages 641 - 652, XP019815449, ISSN: 1573-6830 * |
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